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Eika S. Webb,Peng Liu,Renato Baleeiro,Nicholas R. Lemoine,Ming Yuan,Yaohe Wang.Journal of Biomedical Research,2018,32(5):317-326
Immune checkpoint inhibitors in cancer therapy
Received:December 16, 2016  
DOI10.7555/JBR.31.20160168
Keywordscheckpoint inhibitor, CTLA-4, PD-1, immunotherapy, cancer
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AuthorInstitution
Eika S. Webb Center for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, EC1M 6BQ, UK
Peng Liu Center for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, EC1M 6BQ, UK
Renato Baleeiro Center for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, EC1M 6BQ, UK
Nicholas R. Lemoine Center for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, EC1M 6BQ, UK;Sino-British Research Centre for Molecular Oncology, National Center for International Research in Cell and Gene Therapy, Zhengzhou University, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan , China.
Ming Yuan Center for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, EC1M 6BQ, UK
Yaohe Wang Center for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, EC1M 6BQ, UK;Sino-British Research Centre for Molecular Oncology, National Center for International Research in Cell and Gene Therapy, Zhengzhou University, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan , China.
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Abstract
      In recent years immune checkpoint inhibitors have garnered attention as being one of the most promising types of immunotherapy on the horizon. There has been particular focus on the immune checkpoint molecules, cytotoxic Tlymphocyte antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1) which have been shown to have potent immunomodulatory effects through their function as negative regulators of T cell activation. CTLA-4, through engagement with its ligands B7-1 (CD80) and B7-2 (CD86), plays a pivotal role in attenuating the activation of na?ve and memory T cells. In contrast, PD-1 is primarily involved in modulating T cell activity in peripheral tissues via its interaction with PD-L1 and PD-L2. The discovery of these negative regulators of the immune response was crucial in the development of checkpoint inhibitors. This shifted the focus from developing therapies that targeted activation of the host immune system against cancer to checkpoint inhibitors, which aimed to mediate tumor cell destruction through the removal of coinhibitory signals blocking anti tumor T cell responses.
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